Mixtures Equation Pilot Program to Reduce Animal Testing
Under EPA’s initiative to develop non-animal alternatives for acute toxicity testing (see Letter to Stakeholders on EPA Office of Pesticide Programs' Goal to Reduce Animal Testing), we are announcing the start of a pilot program to evaluate the usefulness and acceptability of a mathematical tool (the GHS Mixtures Equation), which is used in the Globally Harmonized System of Classification and Labeling of Chemicals (GHS). The goal of the pilot is to evaluate the utility and acceptability of the GHS Mixtures Equation as an alternative to animal oral and inhalation toxicity studies for pesticide formulations.
- Instructions for submitting data
- General guide for GHS mixtures equation pilot submissions
- GHS Pilot program information resources
Instructions for Submitting Data
Under this pilot, registrants have the option of submitting mathematical calculations (the GHS Mixtures Equation data), paired with the required acute oral and inhalation acute toxicity data, to support the evaluation of pesticide toxicity. Guidance on the GHS Mixtures Equation is available in the Guidance on the Application of the CLP Criteria (PDF)(246 pp, 1.47MB, About PDF) document (pgs. 250-257) and general guidance on submissions is provided below. Registrants interested in providing data to the Agency using the GHS equation for acute oral and inhalation toxicity estimates, may do so using the following methods and submission routes:
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For Submissions Related to Actions Related to EPA Product Registrations:
The GHS Mixtures Equation data may be attached to an incoming application for product registration or amendment that already has acute toxicity data. In the application cover letter, include the phrase “GHS Mixtures Equation Pilot” in the subject line. Chapter 21 of the Pesticide Registration Manual provides instructions on application submissions.
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For Submissions Not Related to a Current Registration Action:
You may submit the GHS Mixtures Equation data paired with data on acute inhalation or acute oral toxicity, for formulations under the pilot even if there is no incoming action at this time. For these, your submission will follow a different route:
By US Postal Service
Attn: Jenny Tao
U.S. Environmental Protection Agency
Office of Pesticide Programs (7510P)
1200 Pennsylvania Avenue, N.W.
Washington DC 20460-0001
By courier mail (e.g. UPS, FedEx)
Attn: Jenny Tao
Office of Pesticide Programs (7510P)
One Potomac Yard
2777 S. Crystal Drive
Arlington, VA 22202
The Agency recommends that documents containing Confidential Business Information (CBI) be inserted in a separate envelope marked 'Confidential Business Information' inside the mailing envelope.
Registrants also have the option of sending electronic submissions to GHSEquations@epa.gov with “GHS Mixtures Equation Pilot” in the subject line. (Note: Transmittal of CBI over email is not encouraged.)
Any information clearly marked as CBI will be treated as CBI once received by the Agency.
General Guide for GHS Mixtures Equation Pilot Submissions:
GHS Mixtures Equation data submissions should be paired with in vivo animal studies oral and/or inhalation acute toxicity data. Specifically, submissions should contain a table or spreadsheet that includes the following information to support the EPA acute inhalation or acute oral toxicity category for the calculated value based on the mixtures equation:
- Formulation identity (including chemical name, CAS numbers, % by weight for all active and inert ingredients)
- In vivo LD50 and LC50 values for the formulation & associated MRID nos.
- Data source(s)/citations for each LD50 and LC50 value for the individual ingredients and whether the data has previously been reviewed by the Agency
- Calculated value(s) for each formulation
- EPA category for the in vivo study(ies)
- GHS category for the in vivo study(ies)
- EPA category for the calculated value based on the mixtures equation
- GHS category for the calculated value based on the mixtures equation
- A comparison between the calculated endpoints (LD50 and LC50 values) obtained using the GHS Mixtures Equation and the endpoints obtained from animal testing studies
Use this example of a submission template (xlsx) as a guide to formatting data.
GHS Mixtures Equation data that have been previously submitted to other regulatory authorities may be resubmitted to EPA in the original submission format. Upon submission, each study will be associated with an MRID for tracking purposes. GHS Mixtures Equation data are not required to have GLP statements.
Any questions about the GHS Mixtures Equation pilot program can be sent to: GHSEquations@epa.gov, with “Question” in the subject line.